Chiral Imidodiphosphoric Acids‐Catalyzed Friedel–Crafts Reactions of Indoles/Pyrroles with 3‐Hydroxy‐indolyloxindoles: Enantioselective Synthesis of 3,3‐Diaryloxindoles

Abstract

Thef irst enantioselective Friedel-Crafts alkylation of indoles and pyrroles with 3-hydroxy-3-indolyloxindoles to access twon ovelt ypes of 3,3-diaryloxindoles catalyzed by chiral imidodiphosphoric acids hasb een reported. Ar ange of quaternary carbon centered 3,3-diaryloxindoles were synthesized in high yield (up to > 99%) with excellent enantioselectivity (up to 98% ee)a tl ow catalyst loadings (as low as 0.5 mol%). TheF riedel-Crafts reaction between indoles and 3-hydroxy-3-indolyloxindoles is amenable to gram scale syntheses.

Highly Efficient Atom‐Economic Synthesis of Chiral Bis(indolyl)methanes Bearing Quaternary Stereogenic Carbon Centers

“…For example, in 2010, You and co‐workers developed a substitution reaction for 3‐indolylamines with indoles, which led to chiral 3,3′‐BIMs in high yields with moderate enantioselectivities . Subsequently, Zhang's group disclosed efficient methods for the synthesis of optically active 3,3′‐BIMs, in which O ‐trimethylsilyl‐protected 3‐indolylmethanols and 3‐hydroxyindolyloxindoles were used as acceptors to react with indoles by promotion of chiral imidodiphosphoric acids (Scheme a) ,. Recently, Shi and co‐workers reported a highly efficient catalytic asymmetric arylation reaction between substituted indoles and isatin‐derived 3‐indolylmethanols .…”

Organocatalytic Enantioselective Friedel‐Crafts Alkylation Reactions of Pyrroles

“…This strategy, which again employed chiral imidodiphosphoric acids as catalysts, allowed access to a new family of 3,3diaryloxindoles 94. [69] Once optimized, the best reaction conditions involved the use of 2.5 mol% of H 8 -BINOL-derived imidodiphosphoric acid XXXV as the catalyst and 1.5 mol % of HP-β-CD (hydroxypropyl-βcyclodextrin) as an additive, in THF at 55°C. The use of β-cyclodextrin had previously been reported as a supramolecular catalyst to promote substitution reactions of indoles with isatins.…”

Brønsted Acid‐Catalysed Dehydrative Substitution Reactions of Alcohols

“…Shi and co‐workers found that chiral phosphoric acids could catalyse this process to give high yields, [60] although only moderate enantioselectivity was obtained in most cases. Zhang and co‐workers subsequently showed that imidodiphosphoric acid 37 is a highly efficient catalyst for this process, [61] working at low loadings (0.5 mol %), while the addition of 5 Å MS was essential for improving the enantioselectivity without compromising the reaction efficiency (Scheme 27). The reaction scope was demonstrated for substrates bearing a range of substituents within each of the benzenoid rings, while substituted pyrrole nucleophiles are also well tolerated.…”